tbuckley/cabot-search huggingface dataset:
Abstract IA005: On the use of stem cells to generate sarcomas in vitro models
Authors: Judith V.M.G. Boveé
Journal: Clinical Cancer Research (2022)

Abstract Sarcomas are rare cancers arising in soft tissue and bone. They are difficult to diagnose and treat, with 38-48% mortality for this often young age group. It is now generally accepted that molecular changes in cancer open avenues for personalized medicine. However, to achieve this for sarcoma there are several challenges, as representative model systems are scarce. Moreover, sarcomas are heterogeneous and &amp;gt;70 sarcoma types are recognized. A simple dichotomy based on molecular pathways of simple versus complex genomics is often used as a conceptual framework. My group has used mesenchymal stem cells to generate a model for complex genome sarcomas such as osteosarcoma. Murine and canine mesenchymal stem cells (MSCs) can be used to model spontaneous malignant transformation towards sarcomas with complex genomics. These MSCs have an abnormal karyotype, many structural variants and point mutations at whole genome sequencing analysis, and form sarcomas (osteosarcoma, undifferentiated pleomorphic and spindle cell sarcoma) after injection into mice. Cross-species analysis reveals that p53 loss is an early event in sarcomagenesis, and MSCs with a knockout in Trp53 transform earlier compared to wild-type MSCs. In addition, loss of p16Ink4a is shown to be a driver of osteosarcomagenesis: the majority of spontaneously transformed murine MSCs has alterations in p15Ink4b, p16Ink4a, or p19Arf and knockout of these genes in MSCs results in accelerated transformation. Of interest, osteosarcoma cells with defective p16INK4A are sensitive to the CDK4/CDK6 inhibitor Palbociclib, suggesting that a subset of osteosarcoma patients with intact Rb, but defective p16 or overexpression of CDK4 and/or CDK6 (in total 20-23%) might benefit from CDK4/CDK6 inhibition. Bone and soft tissue tumors with a simple genome often carry chromosomal translocations. We have generated a model for pseudomyogenic hemangioendothelioma (PHE), a rare locally aggressive vascular tumor. PHE has a tumor-specific t(7;19)(q22;q13) translocation resulting in a SERPINE1-FOSB fusion. We used CRISPR/Cas9 to generate this fusion in induced pluripotent stem cells (hiPSCs), which were subsequently differentiated into ECs (hiPSC-ECs) to address this. Comparison of parental with PHE hiPSC-ECs shows invasive growth in mice after transplantation, and transcriptome analysis identifies PI3K-Akt and MAPK signaling pathways as possible therapeutic targets. The modified hiPSC-ECs thus recapitulate functional features of PHE and demonstrate how these stem cell based translocation models can be used to understand tumorigenic mechanisms and identify therapeutic targets. Citation Format: Judith V.M.G. Boveé. On the use of stem cells to generate sarcomas in vitro models [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr IA005.
Abstract B008: Investigating the evolution of undifferentiated soft tissue sarcomas in a genetically engineered mouse model
Authors: Jason E. Chan, Jonathan Rub, Carleigh Sussman, Olivera Grbovic-huezo, William D. Tap, Cristina Antonescu, Sam Singer, Doron Betel, Tuomas Tammela
Journal: Clinical Cancer Research (2022)

Abstract Undifferentiated soft tissue sarcomas (USTS) are an aggressive class of sarcomas with few effective treatment options. Because of the rarity of these sarcomas and the paucity of representative disease models, little is known about how they develop. We used single cell transcriptomics to study the initiation and evolution of an USTS in an autochthonous genetically engineered mouse model. We profiled multiple stages of tumor development and identified intermediary cell states that define sarcomagenesis. Interestingly, we identify two discrete evolutionary pathways that arise in parallel in the mouse model. To determine the human relevance of our findings, we are developing machine learning approaches to compare cell states between the mouse model with single-cell transcriptomes that we generated from patient-derived xenografts. This cross-species comparison will uncover core USTS cell states and define their ancestral state transitions. Our ultimate goal is to identify essential molecular features of USTS, which may represent entry points for future therapeutic strategies. Citation Format: Jason E. Chan, Jonathan Rub, Carleigh Sussman, Olivera Grbovic-huezo, William D. Tap, Cristina Antonescu, Sam Singer, Doron Betel, Tuomas Tammela. Investigating the evolution of undifferentiated soft tissue sarcomas in a genetically engineered mouse model [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr B008.
Abstract A014: The novel anti-inflammatory agent GML (GM1-targeted linoleate-containing TLR2 ligand) inhibits sarcoma metastasis to the lung
Authors: Liane Babes, Lauren A. Wierenga, Ngoc-Ha Dan, Xueqing Lun, Kimberly-Ann R. Goring, Stephen M. Robbins, Donna L. Senger
Journal: Clinical Cancer Research (2022)

Abstract Sarcomas are a heterogeneous group of cancers occurring in tissues derived from the mesenchyme. Despite improved treatment strategies that include surgery and broad-based chemotherapeutics, survival of patients with sarcoma remains unchanged in the last 40 years with 5-year overall survival less than 25%. In part, this high rate of mortality can be attributed to the development of pulmonary metastases, a process that occurs in up to 50% of patients. We propose that preventing the occurrence or growth of lung metastases can improve the outcome for many of these patients. Our growing understanding of the dynamic relationship between inflammation and cancer has led to the investigation of anti-inflammatory approaches to treat cancer, including metastasis. Specifically, recent studies suggest a role for neutrophils in cancer metastasis, identifying a promising target for therapeutic intervention. The aim of the present study is to investigate the role of myeloid cells in the metastatic process, and their potential to act as therapeutic targets during the development of lung metastases. Herein we used human and syngeneic osteosarcoma lung metastatic models together with in vitro assays to assess the role of neutrophils in this process. Our results demonstrate that neutrophils are essential to facilitate the development of osteosarcoma pulmonary metastases and that treatment with the novel anti-inflammatory agent GM1-targeted linoleate-containing TLR2 ligand (GML), known to inhibit neutrophil recruitment, diminishes their occurrence. Overall, our results suggest that neutrophils play a role in mediating osteosarcoma lung metastasis and reveal GML as a potential anti-metastatic drug therapy. Citation Format: Liane Babes, Lauren A. Wierenga, Ngoc-Ha Dan, Xueqing Lun, Kimberly-Ann R. Goring, Stephen M. Robbins, Donna L. Senger. The novel anti-inflammatory agent GML (GM1-targeted linoleate-containing TLR2 ligand) inhibits sarcoma metastasis to the lung [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr A014.
Abstract IA029: The origins of leiomyosarcoma: implications for prognosis and defining new therapeutic options
Authors: Rebecca A. Gladdy
Journal: Clinical Cancer Research (2022)

Abstract Introduction: Leiomyosarcomas (LMS) are genetically heterogenous tumors differentiating along smooth muscle lines. Currently, LMS treatment is not informed by molecular subtyping and is associated with highly variable survival. While disease site continues to dictate clinical management, the contribution of genetic factors to LMS subtype, origins, and timing are unknown. Here we analyze 70 genomes and 130 transcriptomes of LMS, including multiple tumor regions and paired metastases, with the goal of defining the molecular origins of LMS and using both computational analysis and functional genomics to define new therapeutic arenas for metastatic disease. Results: Molecular profiling highlight the very early origins of LMS. We uncover three specific subtypes of LMS that likely develop from distinct lineages of smooth muscle cells. Of these, dedifferentiated LMS with high immune infiltration and tumors primarily of gynecological origin harbor genomic dystrophin deletions and/or loss of dystrophin expression, acquire the highest burden of genomic mutation, and are associated with worse survival. Homologous recombination defects lead to genome-wide mutational signatures, and a corresponding sensitivity to PARP trappers and other DNA damage response inhibitors, suggesting a promising therapeutic strategy for LMS. Finally, by phylogenetic reconstruction, we present evidence that clones seeding lethal metastases arise decades prior to LMS diagnosis. Conclusions: In summary, LMS, the catch all-label for any primary malignant smooth muscle neoplasm, encompasses at least three distinct entities. We report that the utility of DNA damage response inhibitors is promising and warrants further exploration. Finally, the molecular evolution and timing of LMS provide a broad window for early intervention and risk stratification for these patients. Citation Format: Rebecca A. Gladdy. The origins of leiomyosarcoma: implications for prognosis and defining new therapeutic options [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr IA029.
A Manual of Hygiene and Sanitation.
Journal: JAMA (1904)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Lectures on Auto-Intoxication in Disease, or Self-Poisoning of the Individual.
Journal: JAMA (1894)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Inaccessibility of Advance Directives on Transfer From Ambulatory to Acute Care Settings
Authors: R. Sean Morrison
Journal: JAMA (1995)

<h3>Objective.</h3> —To investigate the accessibility of patients' previously executed advance directives during an acute hospitalization. <h3>Design.</h3> —Retrospective chart review. <h3>Setting.</h3> —A large metropolitan teaching hospital, a 514-bed skilled nursing facility, a geriatrics ambulatory care clinic, and a geriatrics group practice office. <h3>Patients.</h3> —One hundred fourteen geriatric patients who had previously executed an advance directive. <h3>Main Outcome Measures.</h3> —The medical records of 180 admissions over 3 years, 1991 through 1993, were reviewed for documentation of patients' advance directive status. <h3>Results.</h3> —Twenty-six percent of patients who had previously executed advance directives had their directives recognized during their hospitalization. Of the subgroup of patients who were judged not to have the capacity to make medical decisions during their admissions, 26% (14/53) had their directives recognized. When the advance directive was recognized, it appeared to influence treatment decisions in 12 (86%) of 14 cases. <h3>Conclusions.</h3> —Previously executed advance directives are not accessible when patients are admitted to hospitals for acute illness. When such directives are recognized, they are used to influence medical treatment decisions. Further research is needed to define and overcome barriers to this inaccessibility. (<i>JAMA</i>. 1995;274:478-482)
TGF-β signaling in the tumor metabolic microenvironment and targeted therapies
Authors: Xueke Shi, Jin Yang, Shuzhi Deng, Hongdan Xu, Deyang Wu, Qingxiang Zeng, Shimeng Wang, Tao Hu, Fanglong Wu, Hongmei Zhou
Journal: Journal of Hematology & Oncology (2022)

Abstract Transforming growth factor-β (TGF-β) signaling has a paradoxical role in cancer progression, and it acts as a tumor suppressor in the early stages but a tumor promoter in the late stages of cancer. Once cancer cells are generated, TGF-β signaling is responsible for the orchestration of the immunosuppressive tumor microenvironment (TME) and supports cancer growth, invasion, metastasis, recurrence, and therapy resistance. These progressive behaviors are driven by an “engine” of the metabolic reprogramming in cancer. Recent studies have revealed that TGF-β signaling regulates cancer metabolic reprogramming and is a metabolic driver in the tumor metabolic microenvironment (TMME). Intriguingly, TGF-β ligands act as an “endocrine” cytokine and influence host metabolism. Therefore, having insight into the role of TGF-β signaling in the TMME is instrumental for acknowledging its wide range of effects and designing new cancer treatment strategies. Herein, we try to illustrate the concise definition of TMME based on the published literature. Then, we review the metabolic reprogramming in the TMME and elaborate on the contribution of TGF-β to metabolic rewiring at the cellular (intracellular), tissular (intercellular), and organismal (cancer-host) levels. Furthermore, we propose three potential applications of targeting TGF-β-dependent mechanism reprogramming, paving the way for TGF-β-related antitumor therapy from the perspective of metabolism.
Quality improvement program in Latin America decreases mortality after cardiac surgery: a before-after intervention study
Authors: Omar Asdrúbal Vilca Mejia, Gabrielle Barbosa Borgomoni, Luís Roberto Palma Dallan, Bruno Mahler Mioto, Tarso Augusto Duenhas Accorsi, Eduardo Gomes Lima, Alexandre de Matos Soeiro, Felipe Gallego Lima, Carlos Manuel de Almeida Brandão, Pablo Maria Alberto Pomerantzeff, Luís Alberto Oliveira Dallan, Luiz Augusto Ferreira Lisboa, Fábio Biscegli Jatene
Journal: International Journal of Surgery (2022)
Cerebral Embolic Protection during Transcatheter Aortic-Valve Replacement
Authors: Samir R. Kapadia, Raj Makkar, Martin Leon, Mohamed Abdel-Wahab, Thomas Waggoner, Steffen Massberg, Wolfgang Rottbauer, Samuel Horr, Lars Sondergaard, Juhana Karha, Robert Gooley, Lowell Satler, Robert C. Stoler, Steven R. Messé, Suzanne J. Baron, Julia Seeger, Susheel Kodali, Amar Krishnaswamy, Vinod H. Thourani, Katherine Harrington, Stuart Pocock, Rodrigo Modolo, Dominic J. Allocco, Ian T. Meredith, Axel Linke
Journal: New England Journal of Medicine (2022)

Transcatheter aortic-valve replacement (TAVR) for the treatment of aortic stenosis can lead to embolization of debris. Capture of debris by devices that provide cerebral embolic protection (CEP) may reduce the risk of stroke.
Does Capturing Debris during TAVR Prevent Strokes?
Authors: John D. Carroll, Jeffrey L. Saver
Journal: New England Journal of Medicine (2022)

Transcatheter aortic-valve replacement (TAVR) has become the predominant intervention for the treatment of aortic stenosis.1 The TAVR procedure involves navigation of a large-caliber valve delivery system around the aortic arch and across the stenotic valve. The new valve is deployed and secured in place, and the old valve is crushed behind the frame of the new valve and the aorta. Such interactions between the TAVR valve, the native valve, and the aorta generate debris consisting of fragments of arterial wall, thrombi, valve tissue, and foreign materials that are liberated into the circulatory system (Fig. 1) and can cause stroke.2 Cerebral . . .
ACC/AHA Guidelines for the Clinical Application of Echocardiography
Authors: Melvin D. Cheitlin, Joseph S. Alpert, William F. Armstrong, Gerard P. Aurigemma, George A. Beller, Fredrick Z. Bierman, Thomas W. Davidson, Jack L. Davis, Pamela S. Douglas, Linda D. Gillam, Richard P. Lewis, Alan S. Pearlman, John T. Philbrick, Pravin M. Shah, Roberta G. Williams, James L. Ritchie, Melvin D. Cheitlin, Kim A. Eagle, Timothy J. Gardner, Arthur Garson, Raymond J. Gibbons, Richard P. Lewis, Robert A. O’Rourke, Thomas J. Ryan
Journal: Circulation (1997)
AMA—Fellowship and Residency Electronic Interactive Database Access (AMA-FREIDA):
Authors: Beverley Davies Rowley
Journal: JAMA (1988)

Over the past several years, medical educators and students have been expressing increasing concern about the selection process for graduate medical education programs. The senior year of medical school is a period of intense pressure when medical students must choose a specialty, select a graduate program, and, in some cases, rehearse an internship.<sup>1</sup>Residents who have experienced that process have stated that they did not have enough information to make an informed choice.<sup>1-3</sup> Students seek information about graduate medical education programs from a variety of sources. However, 52% of residents in one study said they did not have available the information they needed to make a decision about a graduate medical education program.<sup>4</sup>One study found the<i>Directory of Graduate Medical Education Programs</i>to be the single most important source of information.<sup>3</sup>Another study found that residents consider published information to be the most important source,
Eye, Ear, Nose and Throat Manual for Nurses.
Journal: JAMA (1925)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Monkeypox plays a similar role like SARS-CoV-2; intensive animal screening is crucial after the first human-to-dog transmission report – Correspondence
Authors: Ranjan K. Mohapatra, Snehasish Mishra, Venkataramana Kandi, Ashish K. Sarangi, Azaj Ansari, Chiranjib Chakraborty, Susanta Kumar Biswal, Kuldeep Dhama
Journal: International Journal of Surgery (2022)
Surgery: Its Principles and Practice. For Students and Practitioners.
Journal: JAMA (1921)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Transcatheter Edge-to-Edge Mitral Valve Repair in Patients With Severe Mitral Regurgitation and Cardiogenic Shock
Authors: Trevor Simard, Sreek Vemulapalli, Richard G. Jung, Andrew Vekstein, Amanda Stebbins, David R. Holmes, Andrew Czarnecki, Benjamin Hibbert, Mohamad Alkhouli
Journal: Journal of the American College of Cardiology (2022)